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Background/Objectives: Streptococcus pneumoniae remains a major cause of morbidity and mortality in Egypt, yet pneumococcal conjugate vaccines (PCVs) are not included in the national immunization program. Recent commitments to domestic vaccine manufacturing and temporary Gavi support create a timely decision context for policymakers to assess whether PCV introduction is cost-effective, affordable, and sustainable within Egypt’s health financing constraints. This study evaluates the cost-effectiveness, budget impact, and return on investment (ROI) of PCV introduction in Egypt. Methods: A deterministic, age-structured dynamic transmission model was developed to estimate the health and economic outcomes of PCV introduction over a 20-year horizon from a healthcare payer perspective. The analysis was conducted in line with the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) guidelines. The model captures direct and indirect effects across all age groups and includes pneumonia, meningitis, non-pneumonia non-meningitis invasive disease, and acute otitis media. Scenarios assessed immediate versus delayed introduction, alternative PCV10-to-PCV13 pathways, and domestic manufacturing price assumptions. Outcomes included deaths averted, incremental cost-effectiveness ratios (ICERs) relative to GDP per capita, budget impact, and ROI using the value of statistical life. Results: Immediate PCV13 introduction was projected to avert 139,451 deaths across all age groups over 20 years, with an ICER of 523.31 USD per DALY averted equal to 0.16 × GDP per capita. The total budget impact was USD 124.9 million per year without Gavi support and USD 120.9 million with support, yielding an ROI of 23.1. Delaying the introduction substantially reduced health gains and economic returns. Pathways involving initial PCV10 introduction followed by transition to PCV13 achieved similar health outcomes with a lower budget impact and higher ROI. Conclusions: PCV introduction in Egypt represents a high-value investment. Immediate introduction maximizes health and economic benefits, while delayed introduction entails substantial opportunity costs. Alternative PCV10-to-PCV13 pathways offer a more affordable route with a similar long-term impact.